Lactate dehydrogenase: relationship with the diagnostic GLIM criterion for cachexia in patients with advanced cancer.

BACKGROUND: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined. METHODS: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011-2016, was retrospectively analysed. LDH values were grouped as <250/250-500/>500 Units/L. Relationships were examined using χ2 test for linear-by-linear association and binary logistics regression analysis. RESULTS: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH > 500 Units/L. LDH was significantly associated with ECOG-PS (p < 0.001), NLR (p < 0.05), mGPS (p < 0.05) and 3-month survival (p < 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p < 0.01), BMI (p < 0.05), skeletal muscle mass (p < 0.01), metastatic disease (p < 0.05), NLR (p < 0.05) and mGPS (p < 0.01). DISCUSSION: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia.

Determinants of quality of life in patients with incurable cancer.

BACKGROUND: Optimizing quality of life (QoL) remains the central tenet of care in patients with incurable cancer; however, determinants of QoL are not clear. The objective of the current study was to examine which factors influence QoL in patients with incurable cancer. METHODS: A multicenter study of adult patients with advanced cancer was conducted in Ireland and the United Kingdom between 2011 and 2016. Data were collected from patients at study entry and included patient demographics, Eastern Cooperative Oncology Group performance status (ECOG-PS), nutritional parameters (the percentage weight loss [%WL]), muscle parameters assessed using computed tomography images (skeletal muscle index and skeletal muscle attenuation), inflammatory markers (modified Glasgow Prognostic score [mGPS]), and QoL data (the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30). The relation between clinical, nutritional, and inflammatory parameters with QoL was assessed using the Spearman rank correlation coefficient and multivariate binary logistic regression. Components of the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30 (physical function, fatigue, and appetite loss) and summary QoL scores were mean-dichotomized for the logistic regression analyses. RESULTS: Data were available for 1027 patients (51% men; median age, 66 years). Gastrointestinal cancer was most prevalent (40%), followed by lung cancer (26%) and breast cancer (9%). Distant metastatic disease was present in 87% of patients. The %WL, ECOG-PS, and mGPS were significantly correlated with deteriorating QoL functional and symptom scales (all P < .001). On multivariate regression analysis, >10% WL (odds ratio [OR], 2.69; 95% CI, 1.63-4.42), an ECOG-PS of 3 or 4 (OR, 14.33; 95% CI, 6.76-30.37), and an mGPS of 2 (OR, 1.58; 95% CI, 1.09-2.29) were independently associated with poorer summary QoL scores. These parameters were also independently associated with poorer physical function, fatigue, and appetite loss (all P < .05). Low skeletal muscle attenuation was independently associated with poorer physical functioning (OR, 1.67; 95% CI, 1.09-2.56), but muscle parameters were not independently associated with fatigue, appetite loss, or QoL summary scores. CONCLUSIONS: The current findings indicate that QoL is determined (at least in part) by WL, ECOG-PS, and the systemic inflammatory response in patients with advanced cancer. Identifying early predictors of poor QoL may allow the identification of patients who may benefit from early referral to palliative and supportive care, which has been shown to improve QoL.

Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation.

Two million infants die each year from infectious diseases before they reach 12 mo; many of these diseases are vaccine preventable in older populations. Pattern recognition receptors represent the critical front-line defense against pathogens. Evidence suggests that the innate immune system does not fully develop until puberty, contributing to impaired response to infection and impaired vaccine responses in neonates, infants, and children. The activity of the pattern recognition receptor family of cytosolic nucleic acid (CNA) sensors in this pediatric population has not been reported. We show that in direct contrast to weak TLR-induced type I IFN in human cord blood mononuclear cells, cord blood mononuclear cells are capable of initiating a potent response to CNA, inducing both antiviral type I IFN and, unexpectedly, proinflammatory TNF-α. A deficiency in Rab11-GTPase endosome formation and consequent lack of IRF3 activation in neonatal monocytes is at least in part responsible for the marked disparity in TLR-induced IFN production between neonatal and adult monocytes. CNA receptors do not rely on endosome formation, and therefore, these responses remain intact in neonates. Heightened neonatal responses to CNA challenge are maintained in children up to 2 y of age and, in marked contrast to TLR4/9 agonists, result in IL-12p70 and IFN-γ generation. CNA sensors induce robust antiviral and proinflammatory pathways in neonates and children and possess great potential for use as immunostimulants or vaccine adjuvants for targeted neonatal and pediatric populations to promote cell-mediated immunity against invasive infectious disease.

A Dairy-Derived Ghrelinergic Hydrolysate Modulates Food Intake In Vivo.

Recent times have seen an increasing move towards harnessing the health-promoting benefits of food and dietary constituents while providing scientific evidence to substantiate their claims. In particular, the potential for bioactive protein hydrolysates and peptides to enhance health in conjunction with conventional pharmaceutical therapy is being investigated. Dairy-derived proteins have been shown to contain bioactive peptide sequences with various purported health benefits, with effects ranging from the digestive system to cardiovascular circulation, the immune system and the central nervous system. Interestingly, the ability of dairy proteins to modulate metabolism and appetite has recently been reported. The ghrelin receptor (GHSR-1a) is a G-protein coupled receptor which plays a key role in the regulation of food intake. Pharmacological manipulation of the growth hormone secretagogue receptor-type 1a (GHSR-1a) receptor has therefore received a lot of attention as a strategy to combat disorders of appetite and body weight, including age-related malnutrition and the progressive muscle wasting syndrome known as cachexia. In this study, a milk protein-derivative is shown to increase GHSR-1a-mediated intracellular calcium signalling in a concentration-dependent manner in vitro. Significant increases in calcium mobilisation were also observed in a cultured neuronal cell line heterologously expressing the GHS-R1a. In addition, both additive and synergistic effects were observed following co-exposure of GHSR-1a to both the hydrolysate and ghrelin. Subsequent in vivo studies monitored standard chow intake in healthy male and female Sprague-Dawley rats after dosing with the casein hydrolysate (CasHyd). Furthermore, the provision of gastro-protected oral delivery to the bioactive in vivo may aid in the progression of in vitro efficacy to in vivo functionality. In summary, this study reports a ghrelin-stimulating bioactive peptide mixture (CasHyd) with potent effects in vitro. It also provides novel and valuable translational data supporting the potential role of CasHyd as an appetite-enhancing bioactive. Further mechanistic studies are required in order to confirm efficacy as a ghrelinergic bioactive in susceptible population groups.

The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.

BACKGROUND: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established. METHODS: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0). RESULTS: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15-24.88, P=0.033; OR=5.23, 95% CI: 1.41-19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09-11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: -4.48 to -1.79%, P<0.001). A loss of SMA ⩾7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02-4.56, P=0.046). CONCLUSIONS: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation.

Poor awareness of risk factors for cancer in Irish adults: results of a large survey and review of the literature.

BACKGROUND: Knowledge of cancer risk factors is unknown in Ireland. An understanding of risk factors could help inform cancer prevention programs. AIMS AND METHODS: A 48-question online survey was designed to gather data to assess levels of public knowledge about cancer risk factors. RESULTS: There were 748 participants (648 women, 100 men). Mean age was 37 years (range: 18-74 years). For the public, 81% were concerned about developing cancer; however, 20% believed that cancer is unavoidable if a family history exists, 27% believed that >50% of cancers are inherited, and 54% believed that 10%-20% of cancers are inherited; 20% were unaware that risk increases with age. The top five risk factors listed by respondents were smoking (87%), diet (76%), genetics (47%), alcohol (42%), and obesity (33%). Only 32% of the public were aware that obesity is a risk factor, and 33% did not think the location of fat was important. Moreover, 29% and 48% believed that risk could be increased by wearing a tight bra and by a blow to the breast, respectively. In addition, 85% and 86% believed that stress and that mobile phones, respectively, "strongly" increase risk; 12% believed that luck is important in avoiding cancer; 35% thought that "detox" diets could reduce risk; and 61% believed that organic food reduces risk. The majority were aware that physical activity of 30 minutes per day can reduce risk. CONCLUSION: A sizable portion of the population is misinformed about cancer risk. Most participants were aware of classic risk factors (e.g., smoking, diet); however, many overestimated risk attributable to genetics, environment, and stress and underestimated age, obesity, and sunlight. One in seven participants believed that lifetime risk of cancer is not modifiable.

Are CT-Derived Muscle Measurements Prognostic, Independent of Systemic Inflammation, in Good Performance Status Patients with Advanced Cancer?

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1-68.1). On univariate analysis, cancer type (p < 0.05) and mGPS (p < 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p < 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p < 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer.

A large, multi-centre prospective study demonstrating high prevalence of malnutrition associated with reduced survival in ambulatory systemic anti-cancer therapy patients.

BACKGROUND & AIMS: The nutritional status of cancer patients is highly variable, and known to impact on clinical outcomes. To date, no large study evaluating the nutritional status of Irish cancer patients has been reported. The aim of this study was to describe the nutritional status, using gold standard methods, of a large cohort of ambulatory oncology patients receiving Systemic Anti-Cancer Therapy and to assess the impact of abnormal body composition phenotypes on survival. METHODS: A prospective study in adults undergoing Systemic Anti-Cancer Therapy for solid tumours enrolled patients between 2012 and 2016. Baseline details were collected incorporating demographics, cancer pathology, lifestyle, body composition (by computed tomography (CT), and inflammatory status. Skeletal muscle index (SMI) and mean muscle attenuation (MA) were obtained from CT images and categorised to low muscle mass and low MA using previously published sex specific cut points. Survival was monitored for a median of 25 months [IQR:10-46 months]. Survival analyses were conducted using multivariate Cox Proportional Hazards Models. RESULTS: Of 1015 patients recruited, 940 patients with an evaluable CT were included in this analysis. Median age was 64 years [IQR 55-71] and 56% were male. Colorectal cancer (28%) and gastro-oesophageal (16%) were the most common diagnoses and 58% of patients had stage IV disease. Despite 56% being overweight or obese (BMI >25 kg/m2), 52% were weight losing and 17% had lost >10% body weight. Cancer Cachexia (CC) was present in 42%, 39% had low muscle mass (MM) (sarcopenia) and 45% had low MA. Overall, 73% of patients exhibited an abnormal body composition (BC) phenotype (≥1 of CC, low MM/MA). Overall survival was significantly lower in those with abnormal BC phenotype, independent of site, stage, sex, ECOG and mGPS (HR: 1.416 [95% CI: 1.069-1.875], p = 0.015). CONCLUSIONS: Malnutrition and abnormal body composition phenotypes are common in cancer, but are often masked by adiposity. Appropriate screening and diagnostic tools should consider this co-presentation of overweight and obesity, alongside muscle depletion. Given that abnormal body composition phenotypes detectable only via CT are associated with reduced survival, these should be more widely employed to identify patients at risk of poor prognosis, and allow potentially more effective, early intervention.

Impact of musculoskeletal degradation on cancer outcomes and strategies for management in clinical practice.

The prevalence of malnutrition in patients with cancer is one of the highest of all patient groups. Weight loss (WL) is a frequent manifestation of malnutrition in cancer and several large-scale studies have reported that involuntary WL affects 50-80% of patients with cancer, with the degree of WL dependent on tumour site, type and stage of disease. The study of body composition in oncology using computed tomography has unearthed the importance of both low muscle mass (sarcopenia) and low muscle attenuation as important prognostic indications of unfavourable outcomes including poorer tolerance to chemotherapy; significant deterioration in performance status and quality of life (QoL), poorer post-operative outcomes and shortened survival. While often hidden by excess fat and high BMI, muscle abnormalities are highly prevalent in patients with cancer (ranging from 10 to 90%). Early screening to identify individuals with sarcopenia and decreased muscle quality would allow for earlier multimodal interventions to attenuate adverse body compositional changes. Multimodal therapies (combining nutritional counselling, exercise and anti-inflammatory drugs) are currently the focus of randomised trials to examine if this approach can provide a sufficient stimulus to prevent or slow the cascade of tissue wasting and if this then impacts on outcomes in a positive manner. This review will focus on the aetiology of musculoskeletal degradation in cancer; the impact of sarcopenia on chemotherapy tolerance, post-operative complications, QoL and survival; and outline current strategies for attenuation of muscle loss in clinical practice.

A national survey of oncology survivors examining nutrition attitudes, problems and behaviours, and access to dietetic care throughout the cancer journey.

BACKGROUND: Attitudes of cancer survivors to nutrition and nutrition care have rarely been captured. A better understanding of their needs based on a review of their experiences would give voice to this patient group (which has rarely been captured) and allow for better planning of nutritional care. AIMS: To conduct a national survey to determine: (1) survivors' experience in relation to nutrition and diet-related problems, (2) perceived importance of the role of nutrition to cancer survivors, (3) the experience of accessing dietetic support, (4) the sources where survivors get nutrition information, and (5) their use of alternative dietary strategies. METHODS: Survivors (any adult ever diagnosed with cancer) who had been diagnosed with or treated for cancer in Ireland within the past 5 years, were asked to complete a 25-item paper-based survey at one of 20 different hospital sites in Ireland. The survey was also hosted online on the websites of major cancer charities. Descriptive statistics were used to examine quantitative data. RESULTS: In total, 1073 valid responses were received (63% female, mean age 57 years (range 18-88)). Breast cancer was the most common (n = 362), followed by colorectal (n = 121). One third of respondents had metastatic disease. Diet-related problems were reported by 45%. Weight loss was experienced by 44% and amongst those, 42% reported they were 'unhappy or worried' by this, while 27% reportedbeing 'delighted/happy' with their weight loss. Muscle loss was noted by 52%, with 20% reporting they had noticed 'a lot' of muscle loss. Nutrition was rated as 'very/extremely' important to cancer care by 89% of respondents, yet 58% reported being asked about dietary issues by their medical team only 'sometimes', 'rarely' or 'never'. Only 39% had been assessed/treated by a registered dietitian (RD) and 74% rated their advice/care as 'very/extremely' helpful. Worryingly, 39% of survivors with involuntary weight loss, and 29% of survivors on a texture modified diet had not received nutritional care from an RD. Overall, 57% of those who did not see an RD said they wanted more dietetic support (access to a helpline/dietitian/additional reliable information). Of concern, 37% of survivors were following or had tried alternative, unproven dietary strategies (e.g. restrictive diets, herbal remedies, juicing or detoxes), and 32% reported avoiding specific foods, e.g. processed meat or dairy. A majority (56%) felt confused by the often conflicting nutrition information available in the media and offered by people around them. CONCLUSIONS: While nutrition is considered highly important by cancer survivors and a high proportion experience potentially serious diet-related problems including weight and muscle loss, fewer than half surveyed had access to a dietitian. Over a third had used at least one alternative dietary strategy, and over half felt confused about nutrition. Comprehensive nutritional screening and referral programmes to oncology dietitians need to be implemented in the ambulatory setting in order to identify and facilitate early management of the nutritional concerns of cancer survivors.

Impact of obesity on surgical and oncological outcomes in the management of colorectal cancer.

INTRODUCTION: Obesity is an established risk factor for colorectal cancer, particularly in males, and may negatively impact on oncologic outcomes. The aim of this study was to examine the impact of body mass index (BMI) on mortality and morbidity, tumour pathology, and overall survival in a consecutive cohort of Irish colorectal cancer patients treated with curative intent. METHODS: A retrospective analysis of BMI data entered prospectively into a comprehensive electronic database of colorectal cancer patients was undertaken. Patients were excluded if they had emergency surgery, previous malignancy or the BMI was not recorded. Analysis was performed comparing genders, obese with non-obese and comparing BMI categories. RESULTS: Of the 414 patients, 10% were underweight (<20 kg/m(2)); 35% were normal weight (20-25 kg/m(2)); 37% were overweight (25-30 kg/m(2)), and 18% were obese (≥ 30.00 kg/m(2)). Obesity overall was not significantly associated with pathological stage (p=0.099) or positive lymph node status (p=0.109) or degree of nodal involvement (p=0.068). Obesity was significantly (p<0.05) associated with more advanced pathological stage, node positivity and degree of nodal involvement in male only and colon cancer only analysis. There was no difference in the overall incidence of major (p=0.244) and minor complications (p=0.078) when comparing obese with non-obese, but pelvic abscesses were more common in obese patients (p=0.037). The underweight cohort had a higher rate of major complications (p=0.041), sepsis (p=0.024) and post-operative death (p=0.006). Survival was equivalent between BMI categories and obese and non-obese groups (p=0.469). CONCLUSION: Obesity was associated with more advanced tumours in males and in colon cancer patients only and with a higher risk of post-operative pelvic abscesses but no significant differences with non-obese cohorts in the main outcome measures of in-hospital mortality, major morbidity and survival. Conversely, the adverse consequences of under-nutrition were highlighted in this study.

The Relationship between ECOG-PS, mGPS, BMI/WL Grade and Body Composition and Physical Function in Patients with Advanced Cancer.

Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/ Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p < 0.001), low skeletal muscle density (p < 0.05), and timed up and go test failure (p < 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p < 0.05) and hand grip strength test failure (p < 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p < 0.05), low visceral obesity (p < 0.01), and low skeletal muscle density (p < 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer.

Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial.

BACKGROUND: Esophagectomy represents an exemplar of controlled major trauma, with marked metabolic, immunologic, and physiologic changes as well as an associated high incidence of complications. Eicosapentaenoic acid (EPA) enriched enteral nutrition (EN) modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the peri-operative period is unclear. OBJECTIVES: To examine the effects of perioperative EPA enriched EN on the metabolic, nutritional, and immuno-inflammatory response to esophagectomy, and on postoperative complications. METHODS: In a double-blind design, patients were randomized to a standard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively (orally) and 21 days postoperatively (jejunostomy). Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21. Postoperative complications were monitored, as well as the acute phase response, coagulation markers, and serum cytokines. RESULTS: Fifty-three patients (28 EPA, 25 standard) completed the study, and both groups were well matched. Serum and peripheral blood mononuclear cell (PBMC) membrane EPA levels were significantly increased in the EPA group. There was no difference in the incidence of major complications. The EPA group maintained all aspects of body composition postoperatively, whereas patients in the standard EN group lost significant amounts of fat-free mass (1.9 kg, P = 0.030) compared with the EPA group [leg (0.3 kg, P = 0.05), arm (0.17 kg, P = 0.01), and trunk (1.44 kg, P = 0.03)]. The EPA group had a significantly (P < 0.05) attenuated stress response for TNFalpha, IL-10, and IL-8 compared with the standard group. CONCLUSIONS: EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a standard EN. These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens.

Accuracy of a Portable Indirect Calorimeter for Measuring Resting Energy Expenditure in Individuals With Cancer.

BACKGROUND: Determining optimal caloric intake for an individual with cancer is complicated by metabolic changes that occur, namely, alterations in resting energy expenditure (REE). There is currently no validated clinically available equation or tool to measure energy expenditure in these patients. METHODS: Patients with newly diagnosed solid tumors underwent REE assessments using the FitMate GS portable indirect calorimeter and reference VMax metabolic cart; both used canopy hoods. REE was also estimated from the Harris-Benedict, Mifflin St. Jeor, and Henry equations for comparison. Data were analyzed using paired samples t-test and the Bland-Altman approach to assess group-level and individual-level agreement compared with the metabolic cart. RESULTS: A total 26 patients (19 males; body mass index: 27.8 ± 5.5 kg/m2 ; age: 62 ± 10 years) participated in the study. Biases for the FitMate GS and both equations were low (ranging from -44 to -92 kcal or -2.3% to -5.1%), indicating good group-level accuracy. The FitMate GS had low bias, but the widest limits of agreement (-28.0% to 21.2%) compared with the 3 equations (Harris-Benedict: -15.8% to 11.2%; Mifflin St. Jeor: -17.1% to 6.9%; Henry: -15.4% to 11.5%). These differences were not due to volume of oxygen, BMI category, or sex. CONCLUSION: FitMate GS performed well on a group level, but its accuracy was poor on an individual level. Further research should develop better equations and validate tools to measure energy expenditure for accurate dietary recommendations for patients at nutrition risk.

Effects of weight loss and sarcopenia on response to chemotherapy, quality of life, and survival.

It has frequently been shown that patients with cancer are one of the largest hospital patient groups with a prevalence for malnutrition. Weight loss is a frequent manifestation of malnutrition in patients with cancer. Several large-scale studies over the past 35 y have reported that involuntary weight loss affects 50% to 80% of these patients with the degree of weight loss dependent on tumor site and type and stage of disease. The aim of this review was to determine the consequences of malnutrition, weight loss, and muscle wasting in relation to chemotherapy tolerance, postoperative complications, quality of life, and survival in patients with cancer. The prognostic impact of weight loss on overall survival has long been recognised with recent data suggesting losses as little as 2.4% predicts survival independent of disease, site, stage or performance score. Recently the use of gold-standard methods of body composition assessment, including computed tomography, have led to an increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation, as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities are highly prevalent (ranging from 10-90%, depending on cancer site and the diagnostic criteria used). Both low muscle mass and low muscle attenuation have been associated with poorer tolerance to chemotherapy; increased risk of postoperative complications; significant deterioration in a patients' performance status, and poorer psychological well-being, overall quality of life, and survival.

Barrett esophagus: prevalence of central adiposity, metabolic syndrome, and a proinflammatory state.

BACKGROUND: Obesity is a risk factor for esophageal adenocarcinoma, with a pathway through inflammation and metaplasia secondary to reflux the dominant hypothesis. The proinflammatory impact of adipocytokines associated with the metabolic syndrome of central adiposity may also be relevant. The objective of this study was to explore this profile in Barrett esophagus. METHODS: Patients with specialized intestinal metaplasia were invited to attend the metabolic syndrome screening where they underwent anthropometry, segmental bioelectrical impedance analysis, and blood pressure measurement, and had blood taken for quantification of fasting lipids, insulin, glucose, C-reactive protein, and adipocytokines. RESULTS: One hundred two patients were studied. Forty-six percent of Barrett patients had metabolic syndrome and 78% were centrally obese. Patients with metabolic syndrome were significantly more obese by body mass index, had a 9.4 cm greater waistline, were more hypertensive, and were insulin resistant with 25% having fasting hyperinsulinemia compared with Barrett patients without metabolic syndrome. Metabolic syndrome was associated with elevated C-reactive protein, leptin, and a trend toward decreased adiponectin levels. Sixty percent of patients with long-segment Barrett had metabolic syndrome, and 92% were centrally obese compared with 23.8% and 62%, respectively (P = 0.007 and 0.005) in short-segment Barrett. Long-segment Barrett was associated with hyperinsulinemia and significantly increased levels of interleukin-6 compared with short-segment Barrett. CONCLUSIONS: The prevalence of metabolic syndrome in Barrett far exceeds population norms, and the syndrome was significantly associated with the length of specialized intestinal metaplasia. The data do suggest that the metabolic syndrome may be relevant to the continuum of metaplasia within the Barrett cohort.

Computed tomography diagnosed cachexia and sarcopenia in 725 oncology patients: is nutritional screening capturing hidden malnutrition?

BACKGROUND: Nutrition screening on admission to hospital is mandated in many countries, but to date, there is no consensus on which tool is optimal in the oncology setting. Wasting conditions such as cancer cachexia (CC) and sarcopenia are common in cancer patients and negatively impact on outcomes; however, they are often masked by excessive adiposity. This study aimed to inform the application of screening in cancer populations by investigating whether commonly used nutritional screening tools are adequately capturing nutritionally vulnerable patients, including those with abnormal body composition phenotypes (CC, sarcopenia, and myosteatosis). METHODS: A prospective study of ambulatory oncology outpatients presenting for chemotherapy was performed. A detailed survey incorporating clinical, nutritional, biochemical, and quality of life data was administered. Participants were screened for malnutrition using the Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), and the Nutritional Risk Index (NRI). Computed tomography (CT) assessment of body composition was performed to diagnose CC, sarcopenia, and myosteatosis according to consensus criteria. RESULTS: A total of 725 patients (60% male, median age 64 years) with solid tumours participated (45% metastatic disease). The majority were overweight/obese (57%). However, 67% were losing weight, and CT analysis revealed CC in 42%, sarcopenia in 41%, and myosteatosis in 46%. Among patients with CT-identified CC, the MUST, MST, and NRI tools categorized 27%, 35%, and 7% of them as 'low nutritional risk', respectively. The percentage of patients with CT-identified sarcopenia and myosteatosis that were categorised as 'low nutritional risk' by MUST, MST and NRI were 55%, 61%, and 14% and 52%, 50%, and 11%, respectively. Among these tools, the NRI was most sensitive, with scores <97.5 detecting 85.8%, 88.6%, and 92.9% of sarcopenia, myosteatosis, and CC cases, respectively. Using multivariate Cox proportional hazards models, NRI score < 97.5 predicted greater mortality risk (hazard ratio 1.8, confidence interval: 1.2-2.8, P = 0.007). CONCLUSIONS: High numbers of nutritionally vulnerable patients, with demonstrated abnormal body composition phenotypes on CT analysis, were misclassified by MUST and MST. Caution should be exercised when categorizing the nutritional risk of oncology patients using these tools. NRI detected the majority of abnormal body composition phenotypes and independently predicted survival. Of the tools examined, the NRI yielded the most valuable information from screening and demonstrated usefulness as an initial nutritional risk grading system in ambulatory oncology patients.

Loss of skeletal muscle during systemic chemotherapy is prognostic of poor survival in patients with foregut cancer.

BACKGROUND: Malnutrition, weight loss, and muscle wasting are common in patients with foregut cancers (oesophagus, stomach, pancreas, liver, and bile ducts) and are associated with adverse clinical outcomes. However, little is known about the changes in body composition that occur in these patients during chemotherapy and its impacts clinical outcomes. PATIENTS AND METHODS: A prospective study of adult foregut cancer patients undergoing chemotherapy between 2012 and 2016 was conducted. Computed tomography images were evaluated for cross-sectional skeletal muscle area (SMA) and adipose tissue area (ATA) at two time points [interval 118 days (IQR 92-58 days)]. Longitudinal changes in SMA and ATA were examined using paired t-tests. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. Cox proportional hazards models were used to estimate mortality hazard ratios for key predictors. RESULTS: A total of 225 foregut cancer patients were included (67% male, median age 66 years). At baseline, 40% were sarcopenic, 49% had low MA, and 62% had cancer cachexia. Longitudinal analysis (n = 163) revealed significant reductions in SMA [-6.1 cm2 (3.9%)/100 days, P < 0.001]. Patients treated with neoadjuvant chemotherapy experienced greater losses in SMA and skeletal muscle mass compared with patients receiving palliative chemotherapy [-6.6 cm2 (95%, confidence interval, CI: -10.2 to -3.1), P < 0.001 and -1.2 kg (95% CI: -1.8 to -0.5), P < 0.001, respectively]. Neither sarcopenia nor low MA at baseline was associated with reduced survival. A loss of SMA >6.0%/100 days (highest fourth) independently predicted overall survival in patients receiving palliative chemotherapy [hazard ratio: 2.66, (95% CI: 1.42 to 4.97), P = 0.002]. CONCLUSIONS: Patients with foregut cancers, particularly those treated with neoadjuvant chemotherapy, experience significant losses of muscle during chemotherapy. A high level of SMA loss is prognostic of reduced survival in patients treated with palliative chemotherapy. Multimodal interventions to stabilize or increase muscle mass and influence outcome warrant further investigation.

Sustained-release multiparticulates for oral delivery of a novel peptidic ghrelin agonist: Formulation design and in vitro characterization.

There is an impetus to provide appropriate sustained release oral delivery vehicles to protect biofunctional peptide loads from gastric degradation in vivo. This study describes the generation of a high load capacity pellet formulation for sustained release of a freely water-soluble dairy-derived hydrolysate, FHI-2571. The activity of this novel peptidic ghrelin receptor agonist is reported using in vitro calcium mobilization assays. Conventional extrusion spheronization was then used to prepare peptide-loaded pellets which were subsequently coated with ethylcellulose (EC) film coats using a fluid bed coating system in bottom spray (Wurster) mode. Aqueous-based EC coating dispersions produced mechanically brittle coats which fractured due to osmotic pressure build-up within pellets in simulated media. In contrast, an ethanolic-based EC coating solution provided robust, near zero-order release in both USP Type 1 and Type 4 dissolution studies. Interestingly, the functionality of aqueous-based EC film coats was restored by first layering pellets with a methacrylic acid copolymer (MA) subcoat, thereby hindering pellet core swelling in acidic media. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) was utilised as a complementary technique to confirm the results seen in USP dissolution studies. Retention of activity of the ghrelinergic peptide hydrolysate in the final encapsulated product was confirmed as being greater than 80%. The described pellet formulation is amenable to oral dosing in small animal studies in order to assess in vivo efficacy of the whey-derived ghrelinergic hydrolysate. In more general terms, it is also suitable as a delivery vehicle for peptide-based bioactives to special population groups e.g paediatric and geriatric.